Manganese(II) complexes of tolfenamic acid or naproxen in polymeric structures or encapsulated in [15-MC-5] manganese(III) metallacrowns: Structure and biological activity

Abstract

The interaction of MnCl2 with the non-steroidal anti-inflammatory drugs tolfenamic acid (Htolf) or naproxen (Hnap) in the presence of salicylhydroxamic acid (H3shi) led- to the formation of the hexanuclear mixed-valence MnIIMnIII5 clusters [Μn6(tolf)2(shi)5(py)6], 1 and [Μn6(nap)(Hsal)(shi)5(py)6], 2 (where H2sal = salicylic acid) which were characterized as 15-metallacrown-5 complexes accommodating the Mn(II) ion and the monoanionic carboxylato ligands tolf−1, nap−1 and Hsal−1. The interaction of Mn(II) with deprotonated naproxen led to the formation of the polymeric Mn(II) complex [Μn(nap)2(CH3OH)]n, 3. All three complexes were characterized by physicochemical and spectroscopic techniques and by single-crystal X-ray crystallography. The in vitro cytotoxic effects of the complexes were evaluated against three cancer cell lines (HeLa, MCF-7 and A549 cells) as well as their combinatory activity with the well-known chemotherapeutic drugs irinotecan, cisplatin, paclitaxel and 5-fluorouracil. The interaction of complexes 1–3 with calf-thymus (CT) DNA and bovine serum albumin (BSA) was investigated in vitro by diverse techniques. In addition, the cytotoxic activity of the previously reported polymeric complex [Μn(tolf)2(DMF)2]n, 4 was also investigated and its behavior towards CT DNA and BSA was compared to that of complexes 1–3.